Heterocyclic organo-tin compounds containing oxygen, sulfur, and tin in the ring



Patented Apr. 28, 1953 HETEROCYCLIC ORGANO-TIN COMPOUNDS v CONTAININGOXYGEN, SULFUR, AND TIN IN THE RING Walter A. Gregory, Wilmington, DeL,assignor to E. I. du Pont de Nemours and Company, Wilmington, Del., acorporation of Delaware No Drawing Application December 27, 1950, SerialN0. 203,029

This invention relates to novel organotin compounds containingtin-sulfur linkages, and more particularly to2,2-dia1kyl-l-oxa-2-stanna-3-th1- acyc1opentan-5-one,2,2-dia1kyl-1-oxa-2-stannao=ox where R. is an alkyl radical containingfrom one to six carbon atoms and X is a divalent radical selected fromthe group consisting of methylene (Jim) ethylene H (CH2-CH2'-) andaminoethylene in which the amino group is attached to the carbon in the5-position 5 4 (I) H- 0 Hr) According to the present invention it hasbeen found that the novel compounds represented graphically by Formula 1can be prepared by reacting a compound of formula:

A R2ShY where Y is 'a member of the group consisting of oxygen,dihalogen, dinitrate, and diacetate, and R has the same significance asin Formula 1, with a compound selectedfrom the group consisting ofthioglycollic acid, beta-mercaptopro pionic acid and cysteine.

The organotin compounds which can be employed in the processes of myinvention include dialkyltin dinitrates, dialkyltin diacetates,dialkyltin oxides and dialkyltin dihalides, preferably the dialkyltindichlorides. Each of the alkyl groups in the dialkyltin compounds shouldbe identical and should oontainnot more than six carbon atoms. The alkylgroups, which include methyl, ethyl, propyl, butylyamyl and hexyl, arepreferably straight chained but branched chained alkyls'such-as, forexample, isopropyl,'isobutyl,

8 Claims. (Cl. 260-429) sec-butyl and isoamyl, can be used. Particularlypreferred of the dialkyltin compounds for my invention are those of thedibutyl series. Typ products of the butyl series which are available onthe market include dibutyltin oxide, dibutyltin dichloride anddibutyltin diacetate.

If desired, the commercially available dialkyltin compounds may befurther purified prior to use in my novel processes. For example, thepurification of dibutyltin oxide is preferably carried out byreprecipitating it from a filtered aqueous nitric acid solutioncontaining commercial dibutyltin oxide by the slow addition of ammoniumhydroxide.

It will be understood that all of the starting materials used in mynovel processes can be synthesized from known chemicals. By way ofillustration, a diallryltin dihalide can be prepared by reacting theappropriate Grignard reagent with tin tetrahalide. The dialkyltindihalide is converted to the corresponding diacetate by reaction withammonium hydroxide to form dialkyltin oxide which in turn is reactedwith acetic acid. A preferred synthetic route to the dialkyltindiacetate involves the reaction of dialkyltin dihalide with sodiumacetate.

The reaction between a compound of Formula 2 and a carboxy substitutedthiol, selected from the group consisting of thioglycollic acid,betamercaptopropionic acid and cysteine, to produce my novel products ispreferably carried out at room temperature by thoroughly mixing anacidic solution of the dialkyltin compound of Formula 2 with the thiol-An aqueous solution of the thiol hydrochloride is preferably employed.The crystalline precipitate which separates can be collected byfiltration and washed with a water-immiscible organic liquid, such asdiethyl ether. Even without further refinement of the product, analysisof it conforms closely vto the calculated value. If desired, the solidproduct may be fur--' ther purified by recrystallization, preferablyfrom glacial acetic acid.

Alternatively, the crystalline precipitate which separates out under theabove described conditions can be dissolved prior to isolation by theaddition to the reaction mixture of a Weak base, preferably ammoniumhydroxide. The material which is insoluble in the basic solution isremoved by filtration. The filtrate is neutralized with acid, yieldingthe desired White crystalline prod not of the invention.

My novel products characterized by their white crystalline structurepossess noteworthy antibacterial properties. They are especiallysuitable for use as toxicants for microorganisms, particularly forbacteria and fungi. The compounds of my invention are also effective inreducing the incidence of cecal coccidiosis of chickens, a diseasecaused by a microscopic protozoan parasite, Eimeria tenella.

The invention is -iflu'strated by the following examples:

EXAMPLE 1 2,2-dibutyZ-1-era-2-sta1ma-B-thiuwclopantan- -one A solutionof parts of commercial dibutyltin diacetate in 26 parts of glacial:acetic acid stirred during the addition of 26 par-ts =of thieglycollicacid. Stirring of the mixture is continued until no further precipitateforms. The white crystalline product is filtered, washed -.with diethylether, and then recrystallized from 168 parts of glacial acetic acid.The purified product consisting of2,2-dibutyl-l-oxa-2-stanna-3-thiacyclopentan-5-one has a melting pointof 185- '1 "87 C. and possesses the following formula:

(C4Hv)2 Analys'is "calculated for CmHmOS'Sn; .8, 9.91. Found:S,T9.'94,,10;0'8.

Using the process of Example .1, 2,2-dipropyl-1-oxa-2-stanna-3-thiacyclopentan-5-one, 2,2- diisoamyl 1 oxa 2 stanna 3thiacyclopentan 5 one, 2,2 dihexyl 1 .oxa .2 stanna-3-thiacyclopentan-3one and the like can be readily prepared by merely substituting theappropriate dialkyltin compound of Formula 2 ior the dibutyltindiacetate of Example 1.

5 amino 2,2 dibutyl 1 oxa 2 stanna J3 th'iacyclo'hexan f6 one To.astirred solution of 24.9 parts of dibutylt'in oxide in 150 ,parts ofwater containing 45 parts of nitric acid (specific gravity 1.42, 71% :byweight) there is added a solution of 315 parts of cysteine hydrochloridein 50 parts of water. A White crystalline precipitate separates. Thereaction mixture then made basic :by the slow addition of ammoniumhydroxide, whereupon the crystals dissolve and a noncrystallineprecipitate separates. The mixture is made more strongly .basic causinthe greater portion of the precipitate to dissolve. The resultingsolution is filtered, and the filtrate neutralized with glacial aceticacid. The desired product, 5- amino 2,2 dibutyl 1 oxa 2 stanna 3-thiacyclohexan-fi-one, :separates from the solution. This product, whichhas the formula shown below, decomposes at a temperature "of 205-F7 C.

.Analysis calculated for C11H23NOzSSn: N, 3.98. Found: N, 3.96,-4.08.

2,2 dibutyl 1 oxa 2 stanna 3 -thiacyclo'hex'an-ii one can be prepared bymerely substituting beta-mercaptopropionic acid for cysteinehydrochloride in the process of Example 2.

Similarly, other compounds such as 2,2 dimethyl 1 -oxa 2 stanna 3thiacyclohexan 6 .one,

2,2 diethyl 1 -oxa :2 stanna B thiacyclohexan 6 one,

2,2-di-n-propyl-1-oxa-2-stanna-3- thiacyclohexan 6 one,

22 oi -"'isopropy1 1 oxa 2 stanna 3 -.thi'acyclohexan 6 one,

2,2 di --sec 'bu'tyl 1 oxa 2 stanna 3 thiacyclohexan .6 one,

2,,'-2-.di -11 -:amyl -11 oxa 2 stanna 3- thiacyclohexan 6 (0118,

2,2 di isoamyl 1 oxa 2 stanna 3 thiacyclohexan '6 one,

2,2 di ter amyl 1 oxa 2 stanna 3- thiacyclohexan 6 one,

2,2-d1-n-hexyl-1-oxa-2-stanna-3- :thiacyclohexan 6 one,

2,2 di=- isohexyl 1- oxa 2 stanna .3 thiacyclohexan .6 one,

5 amino 2,2 dimethyl 1 oxa- 2 -stanna- 3 thiacyclohexan 6 one,

.5 amino 2,2 diethyl 1 -.oxa -.2 --stanna 3 thiacyclohexan 6 one,

,5 amino 2,,2 di n gpropyl- 11 oxa- 2 stanna 3 thiacyc'lohexan *6 one,

- amino 2,2 :di lisopropyl ,1 oxa 2 stanna .3 thiacyclohexan E6 one, 5amino 2,2 di sec butyl 1 oxa stanna 3 thiacyclohexan 6 one,5-amino-2,2-di-'n-arnyl-1-oxa-2- stanna 3 thiacyclohexan 6 one,

5 amino 2,2 di isoamyl 1 oxa 2 stanna 3 thiacyclohexan 6 one,

5 amino 2,2 d'i ter amyl 1 oxa "stanna -13 thiacyclohexan 6 one,

5 amino 2,2 di n 'hexyl '1 *oxa 2 stanna 3 thiacyclohexan 6 one,

5 amino 2,2 di isohexyl 1 oxa 2 stanna 3 thiacyclohexan 6 one,

can be made by the method of Example 2 "by simply substituting theappropriate dialkyltin compound of Formula 2 for the dibutyltin oxide ofExample 2.

I claim: 1. A compound represented Joy the formula:

(3)4 t d es at where R, is an alkyl radical containing not more than sixcarbon atoms and X is a divalent radical selected from the groupconsisting of methyl- 'ene ethylene and amino ethylene in which theamino group is attached to the carbon in the .5-position 2. 2,2-dibutyll 0X2. 2 stanna -I3-- thiacyclopentan-fi-one, a compound having the formula 3. 2,2-dicuty1 1 oxa 2 stanna 3 thiacyclchexan-fi-one, a compoundhaving the formula i. 5 amino 2,2 dibutyl 1 oxa 2 stanna 3thiacyclohexan 6 one, a compound having the formula 5. A process for theproduction of a compound of claim 1 which comprises reacting a compoundof formula,

RzSIlY Where R is an alkyl radical containing not more than six carbonatoms, and Y is a member of the group consisting of oxygen, dihalogen,dinitrate, and diacetate, with a compound selected from the groupconsisting of thioglycollic acid, beta-mercaptopropionic acid andcysteine.

6. A process for the production of 2,2-dibutyl-1-oxa-2-stanna-3-thiacyclopentan-5-one, a compound having the formulawhich comprises reacting dibutyltin diacetate with thioglycolic acid inthe presence of glacial acetic acid.

7. A process for the production of 2,2-dibuty1-1-oxa-2-stanna-3-thiacyclohexan-G-one, a compound having the formulawhich comprises reacting beta-mercaptopropicnic acid with dibutyltinoxide in an acidic medium.

8. A process for the production of 5-amino- 2,2 dibutyl 1 oxa 2 stanna 3thiacyclohexan 6 one, a compound having the formula which comprisesreacting cysteine hydrochloride with dibutyltin oxide in a. dilutenitric acid medium.

WALTER A. GREGORY.

References Cited in the file of this patent C. A., v01. 28, page 62.

Mann, The Chemistry of I-Ieterocyclic Compounds-The HeterocyclicDerivative of Phosphorus, Arsenic, Antimony, Bismouth and Silicaon-page151, Interscience Publishers Inc., New York, 1950, see also Ber. 39,1356 (1906).

1. A COMPOUND REPRESENTED BY THE FORMULA: